Pharm Block 2 (Antithrombotc Drugs)

-inhibition of the synthesis of vitamin K dependent functional clotting factors II, VII, IX and X as well as anticoagulant protein C in the liver.

žWarfarin, Dicumoral, Phenindione

It is a Anti-coagulant that works through inhibiting the synthesis of Vitamin K depentents factors.

• taken orally
• Effect is delayed 3-5 days. (4-5 half lives for the proteins to ne excreted from the plasma)

may cause an initial Coagulation so you might want to use with Heparin.

• -Bleeding is Common--- Monitor via PT or INR
• -Skin Necrosis, purple toes and alopecia
• Fetal Warfarin syndrome
• - Some other Antibiotics can exagerate the effects of Warfarin (inhibit Vit K reductase).

• -Stop Warfarin
• -The Antidote is Vitamin K (K1 phytonadione)

If the hemorrhage is serious you can give Plasma Clotting factors II,VII,IX and x

Intrinsic- heparin is used to block it, monitor with PTT.

Extrinsic- Warfarin is used to block it and PT is used to monitor.

These are plasminogen activators which convert plasminogen into plasmin that catalyzes the degradation of fibrin. Used to lyse preformed clots.

Streptokinase, Urokinase, t-PA

Use them in Pulmonary Emboli and MI

• žNon-selective plasmin production:
• 1.Streptokinase
• 2.Urokinase

• žClot (fibrin) selective;
• 1.Recombinant tpa (Alteplase)

• Where is it from? Hemolytic Stretococci
• is it antigenic? Yes
• Is it specific? No
• long or short half life? Longer (30 min)

• Where is it from? Renal cells
• is it antigenic? NO
• Is it specific? NO
• long or short half life? Short

Alteplase, Teteplase and Tenecteplase

• Where is it from? Recombinant DNA
• is it antigenic? NO
• Is it specific? YES
• long or short half life? Short

Aminocaproic acid, Tranexamic acid

- they acts by binding plasminogen and inhibiting its activation to plasmin

- Excessive or abnormal menstral Bleeding and Post Delivery bleeding.

• 2. Phosphdiesterase Inhibitors: Dipyridamole, Cilastazol.
• 3. ADP pathway Inhibitors:Ticlopidine, Clopidogrel.
• 4.GLYCOPROTEIN II b / III a RECEPTORS INHIBITORS Abciximab, Eptifibatide, Tirofiban

5HT, Epinephrine, PAF, Collagen, ADP, TXA2, Vasopressin, thrombin

it is an anti-platelet drug

• -works through Irreversible inactivation of TXA2 synthetase in the platelets.
• -žLow dose spares endothelial synthesis of PGI-2 and thus better anti-platelet activity.

žGastric bleeding is a disadvantage.

• It is an a very weak anti-platelet drug.
• Usually is used in Combination with other anti-platelet drugs. Example: it is used with aspirin in prevention of thromboembolism in prosthetic heart valves and stroke

They are Anti-platelet Drugs

• - blocks purinergic (ADP) receptors on the platelets
• - It causes less G bleeding then Aspirin.
• - Ticlopidine is associated with neutropenia and thrombocytopenia.

ABCIXIMAB, EPTIFIBATIDE,TIROFIBAN

- Binds to IIb / IIIa receptors on platelets and block the binding of fibrinogen and thus inhibits aggregation of platelets.

• - Used in acute coronary syndrome and coronary angioplasty.
• - Heparin / aspirin can be given with it.